Polyglycolic acid is a resin material excellent in biodegradability, gas barrier properties, strength, etc., and is used in a wide variety of technical fields as medical polymeric materials for surgical sutures, artificial skins, etc.; packaging materials for bottles, films, etc.; and resin materials for various industrial products such as injection-molded products, fibers, deposition films and fishing lines.
In order to use the polyglycolic acid as resin materials for various technical fields, the polyglycolic acid is required to have a polymerization degree suitable for the respective uses. In addition, reduction in production cost is an important problem for developing new uses of the polyglycolic acid. In order to solve these requirement and problem, the mass production, high purification and reduction in cost of glycolide used as a monomer are strongly required.
The polyglycolic acid is a polymer having a repeating unit of a structure formed by dehydration polycondensation of glycolic acid. However, the process by the dehydration polycondensation of glycolic acid only provides low-polymerization degree polyglycolic acid having a weight-average molecular weight of 20,000 or lower. The low-polymerization degree polyglycolic acid is generally called a glycolic acid oligomer and insufficient in strength, melt processability, gas barrier properties, etc. The low-polymerization degree polyglycolic acid is too fast in degradation rate under a natural environment and in vivo and cannot satisfy the requirement of durability when it is applied to many uses.
According to the process by the dehydration polycondensation of glycolic acid, it is difficult to control the polymerization degree of the resulting polyglycolic acid. In particular, it is extremely difficult at the present state of the art to synthesize high-polymerization degree polyglycolic acid. It is also difficult to synthesize high-polymerization degree polyglycolic acid even when an alkyl ester of glycolic acid is used as a monomer to conduct dealcoholization-polycondensation.
According to a process of subjecting glycolide to ring-opening polymerization, it is easy to control of the polymerization degree of the resulting polyglycolic acid, and high-polymerization degree polyglycolic acid can be synthesized. The glycolide is a cyclic ester compound having a cyclic dimeric structure formed by eliminating two molecules of water from two molecules of glycolic acid. However, glycolide cannot be synthesized even by a dehydration reaction of glycolic acid, but low-polymerization degree polyglycolic acid (glycolic acid oligomer) is only obtained.
As a production process of glycolide, a process of depolymerizing a glycolic acid oligomer is representative. Specifically, glycolic acid is polycondensed according to the following reaction formula 4:
to synthesize a glycolic acid oligomer having a low polymerization degree. The glycolic acid oligomer is then depolymerized according to the following reaction formula 5:
to synthesize glycolide. When the glycolide is subjected to ring-opening polymerization, polyglycolic acid can be produced according to the following reaction formula 6:
According to the ring-opening polymerization of glycolide, high-polymerization degree polyglycolic acid can be synthesized, and the polymerization degree thereof can be easily controlled.
Various proposals have been made on a process for synthesizing glycolide by depolymerization of a glycolic acid oligomer. Among these, a solution phase depolymerization process has been proposed as a process suitable for mass production of glycolide. The solution phase depolymerization process is a process, in which a mixture containing a glycolic acid oligomer and a high boiling polar organic solvent is heated to form a solution phase of the glycolic acid oligomer, and the heating is continued in that state to conduct depolymerization. When there is need to raise the solubility of the glycolic acid oligomer in the high boiling polar organic solvent, a solubilizing agent is contained in the mixture.
Japanese Patent Application Laid-Open No. 9-328481 (Patent Literature 1) has proposed a production process of a cyclic dimeric ester, in which an α-hydroxycarboxylic acid oligomer such as a glycolic acid oligomer is heated in a high boiling polar organic solvent to dissolve the oligomer, the heating is continued in that state to conduct depolymerization, a cyclic dimeric ester formed is distilled out together with the high boiling polar organic solvent, and the cyclic dimeric ester (for example, glycolide) is recovered from the distillate.
Domestic Republication of WO 02/014303 (Patent Literature 2) has proposed a production process of a cyclic ester, in which a mixture containing an aliphatic polyester such as low-molecular weight polyglycolic acid and a specific polyalkylene glycol ether is heated to a temperature at which depolymerization of the aliphatic polyester takes place to form a homogeneous solution phase, the aliphatic polyester is depolymerized in this state, a cyclic ester formed by the depolymerization is distilled out together with the polyalkylene glycol ether, and the cyclic ester (for example, glycolide) is recovered from the distillate.
Japanese Patent Application Laid-Open No. 2004-523596 (Patent Literature 3) discloses a production process of glycolide, in which a depolymerization reaction is continuously conducted while continuously or intermittently pouring a glycolic acid oligomer or a mixture of a glycolic acid oligomer and a high boiling polar organic solvent into a depolymerization reaction system containing a glycolic acid oligomer and a high boiling polar organic solvent.
According to the processed disclosed in Patent Literatures 1 to 3, the depolymerization reaction can be stably performed in addition to the fact that glycolide can be mass-produced. According to the process disclosed in Patent Literature 3 in particular, lowering of the rate of production of glycolide and the formation of tar, which are caused by impurities accumulated in the depolymerization reaction system, can be inhibited even when the depolymerization reaction is continuously conducted in the same reaction vessel.
In the processes disclosed in Patent Literatures 1 to 3, a high boiling non-basic compound is used as a solubilizing agent, the solubility of the glycolic acid oligomer in the high boiling polar organic solvent can be raised, and moreover the rate of production and yield of glycolide can be improved.
When a depolymerization reaction is continuously performed in the same apparatus while continuously or intermittently pouring a glycolic acid oligomer into the depolymerization reaction system containing a glycolic acid oligomer and a high boiling polar organic solvent, the operation can be continuously conducted over a relatively long period of time. However, it has been found that when the operation is continuously conducted for several months or longer by this process, the blocking of a line through a piping, a heat exchanger, etc. is caused.
In the depolymerization reaction, the mixture containing the glycolic acid oligomer and the high boiling polar organic solvent in the reaction vessel is heated to conduct depolymerization, and glycolide formed is distilled out together with the high boiling polar organic solvent. The co-distillate is guided to the outside of the depolymerization reaction system via the line through the piping, heat exchanger, etc. The depolymerization reaction is generally performed under reduced pressure. The co-distillate is cooled by the heat exchanger and liquefied. Glycolide is recovered from the liquid co-distillate. The high boiling polar organic solvent contained in the co-distillate is refluxed into the depolymerization reaction system. A glycolic acid oligomer is newly added into the depolymerization reaction system for supplementing the glycolic acid oligomer consumed by the depolymerization.
According to this process, the operation can be continuously conducted for a relatively long period of time. However, it has been found that when the continuously operating period is extended to several months or longer, impurities contained in the depolymerization reaction system act as a polymerization initiator to oligomerize a part of glycolide formed to block the line. When the line is blocked, the predetermined degree of reduced pressure cannot be retained, and soon the continuation of the operation becomes impossible. Therefore, the operation must be stopped after a certain period of time has elapsed to clean the whole apparatus including the line through the piping, heat exchanger, etc. It takes about 2 to 3 weeks for the cleaning though it varies according to the scale and structure of the apparatus. Frequent stopping of the operation and the cleaning treatment directly connect with increase in production cost.
The conventional glycolide obtained by the depolymerization of the glycolic acid oligomer is insufficient in purity and called crude glycolide. Glycolide used as a monomer for ring-opening polymerization is required to have a high purity of 99.9% or higher. Therefore, the crude glycolide obtained by the depolymerization is highly purified by purification treatments such as recrystallization and washing. When the purity of the crude glycolide is low, blocking of the line may be caused in some cases in addition to the fact that purification cost cannot be reduced.
The main cause of the line blocking in the depolymerization reaction is presumed to be attributable to the fact that impurities contained in a distillate distilled out of the depolymerization reaction system act as a polymerization initiator to oligomerize glycolide formed by the depolymerization and distilled off in the course of the line to block the line, and this oligomer attaches to the surfaces of respective parts of the apparatus. In fact, the crude glycolide obtained by the depolymerization contains various impurities.
When the crude glycolide obtained by the depolymerization is analyzed, water and various organic acids are detected as principal impurities. Glycolic acid, a linear glycolic acid dimer, a linear glycolic acid trimer, etc. are detected as the organic acids. Such impurities are presumed to include those contained in the glycolic acid oligomer and formed during the depolymerization reaction of the glycolic acid oligomer.
These impurities are presumed to not only react with glycolide formed even in the depolymerization reaction system containing the glycolic acid oligomer and the high boiling polar organic solvent to increase the amount of the impurities, but also cause ring-opening polymerization of the glycolide in the course of the line to form the cause of the line blocking during the continuous operation over a long period of time.